Treatment approaches to macrophage activation syndrome in real life and priorities for future research: results from the international METAPHOR project

OBJECTIVE: Macrophage Activation Syndrome (MAS) is a rare, life-threatening hyperinflammatory condition complicating rheumatologic diseases, most commonly Still's disease (SD). Despite increasing awareness and emerging recommendations, MAS treatment remains heterogeneous worldwide. The METAPHOR project aimed to describe real-life therapeutic strategies for MAS, exploring differences across underlying diseases, geographic regions, physician subspecialties, and drug availability. METHODS: An international web-based survey was developed by a multidisciplinary expert panel together with a patient representative, following a systematic literature review. The survey was anonymously completed through PReS/PRINTO and the Histiocyte Society networks (October-December 2023). Treatment strategies for MAS across different rheumatologic contexts were explored. Responses were analyzed descriptively and stratified by geography, subspecialty, clinical experience, and underlying disease. RESULTS: -line therapy across all MAS subtypes (for 44% of clinicians as monotherapy). Anakinra, ciclosporin, and intravenous immunoglobulins were the most frequently combined agents. However, their use varied markedly by underlying disease and geographical region, with anakinra preferentially used in SD-MAS. Striking global disparities in drug availability, particularly for anakinra and emapalumab, significantly influenced treatment choices and were associated with increased reliance on steroid monotherapy. CONCLUSION: MAS management remains highly heterogeneous worldwide. While glucocorticoids remain foundational, reducing steroid reliance through equitable access to immunomodulatory therapies and advancing mechanism-based strategies represent critical priorities in optimizing MAS care.

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Journal
Arthritis & Rheumatology
Published
2026-09-21
DOI
https://doi.org/10.1002/art.70348
Primary Topic
Autoimmune and Inflammatory Disorders Research
Type
article
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article

Treatment approaches to macrophage activation syndrome in real life and priorities for future research: results from the international METAPHOR project

Grant S. Schulert, Francesca Minoia, Jordi Antón, Angelo Ravelli et al.
Arthritis & Rheumatology
Autoimmune and Inflammatory Disorders Research
article

Treatment approaches to macrophage activation syndrome in real life and priorities for future research: results from the international METAPHOR project

Grant S. Schulert, Francesca Minoia, Jordi Antón, Angelo Ravelli, Randy Quentin Cron, AnnaCarin Horne, Mao Mizuta, Dirk Foell, Merav Heshin‐Bekenstein, Claudia Bracaglia, Paul A. Brogan, Marco Gattorno, Greta Rogani, Fabrizio De Benedetti, Scott Canna, Seza Özen, Remco G. A. Erkens, Rashmi Sinha, Raju Khubchandani, Sebastiaan Vastert, Christiaan Scott, Alexei Grom, Nicolino Ruperto, Shanmuganathan Chandrakasan, Francesco Baldo, Pierre Quartier, Marija Jelusic, Masaki Shimizu, Joost F Swart
article en

Abstract

OBJECTIVE: Macrophage Activation Syndrome (MAS) is a rare, life-threatening hyperinflammatory condition complicating rheumatologic diseases, most commonly Still's disease (SD). Despite increasing awareness and emerging recommendations, MAS treatment remains heterogeneous worldwide. The METAPHOR project aimed to describe real-life therapeutic strategies for MAS, exploring differences across underlying diseases, geographic regions, physician subspecialties, and drug availability. METHODS: An international web-based survey was developed by a multidisciplinary expert panel together with a patient representative, following a systematic literature review. The survey was anonymously completed through PReS/PRINTO and the Histiocyte Society networks (October-December 2023). Treatment strategies for MAS across different rheumatologic contexts were explored. Responses were analyzed descriptively and stratified by geography, subspecialty, clinical experience, and underlying disease. RESULTS: -line therapy across all MAS subtypes (for 44% of clinicians as monotherapy). Anakinra, ciclosporin, and intravenous immunoglobulins were the most frequently combined agents. However, their use varied markedly by underlying disease and geographical region, with anakinra preferentially used in SD-MAS. Striking global disparities in drug availability, particularly for anakinra and emapalumab, significantly influenced treatment choices and were associated with increased reliance on steroid monotherapy. CONCLUSION: MAS management remains highly heterogeneous worldwide. While glucocorticoids remain foundational, reducing steroid reliance through equitable access to immunomodulatory therapies and advancing mechanism-based strategies represent critical priorities in optimizing MAS care.

Arthritis & Rheumatology
Tokyo Medical and Dental University (JP), Cincinnati Children's Hospital Medical Center (US), Hôpital Necker-Enfants Malades (FR), Hospital Sant Joan de Déu Barcelona (ES), Karolinska University Hospital (SE), Children's Hospital of Philadelphia (US), University Hospital Centre Zagreb (HR), University of Ottawa (CA), University of Cape Town (ZA), Utrecht University (NL), Université Paris Cité (FR), Tel Aviv Sourasky Medical Center (IL), Great Ormond Street Hospital (GB), Istituto Giannina Gaslini (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Karolinska Institutet (SE), University Medical Center Utrecht (NL), University of Alabama at Birmingham (US), University Hospital Münster (DE), Istituto Ortopedico Gaetano Pini (IT), Bambino Gesù Children's Hospital (IT), Kobe Children's Hospital (JP), Children's Healthcare of Atlanta (US), SRCC Children’s Hospital (IN), University College London (GB), Hacettepe University (TR), University of Milano-Bicocca (IT)
Partnerships for the goals
Openalex Percentile: Top 11%
Autoimmune and Inflammatory Disorders Research
DOISourceOpenAlex
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